Agnostic Therapy in Rare Solid Tumors
- Conditions
- FibrosarcomaUrachal CancerParathyroid CarcinomaFibrolamellar CarcinomaAngiosarcomaSecretory Carcinoma of BreastAnal NeoplasmsMetaplastic Breast CarcinomaTranslocation Renal Cell CarcinomaCarcinosarcoma
- Interventions
- Registration Number
- NCT06638931
- Lead Sponsor
- Instituto do Cancer do Estado de São Paulo
- Brief Summary
The ANTARES study is a phase II basket trial designed to evaluate the tissue-agnostic efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or metastatic rare tumors.
The study aims to treat rare malignancies with PD-L1 expression (CPS ≥ 10), regardless of the tumor's tissue type or location. Patients who have not responded to standard treatments will be included, and treatment will last for up to 12 months. The study will assess objective response, progression-free survival, and biomarkers such as PD-L1, ctDNA, and microvesicles, in a multicenter collaborative effort to provide innovative therapeutic options for this underrepresented population
- Detailed Description
The ANTARES study is a phase II "basket" trial designed to evaluate the tissue-agnostic efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or metastatic rare tumors. A "basket" trial is an innovative type of clinical trial where patients with different types of cancers, but sharing a common molecular feature (in this case, PD-L1 expression), are treated with the same therapy, regardless of the tumor's site of origin. This approach allows for the evaluation of treatments targeting specific molecular characteristics, independent of the primary cancer type.
Rare tumors, as defined by the World Health Organization (WHO), have an incidence of fewer than six cases per 100,000 people per year. Although each rare cancer type is individually uncommon, collectively they account for 25-30% of all malignancies and are often underrepresented in clinical trials due to recruitment challenges and limited funding. As a result, patients with rare cancers generally have a poorer prognosis compared to those with more common tumors.
In this study, patients with advanced or refractory rare malignancies expressing PD-L1, with a combined positive score (CPS) of ≥10, will be treated with nivolumab. Treatment will be administered until disease progression or for a maximum duration of 12 months, aiming to assess the efficacy and safety of this tissue-agnostic immunotherapy approach. Efficacy will be measured according to RECIST v1.1 criteria, with objective response as the primary endpoint. Additionally, the study will assess response biomarkers, including PD-L1, circulating tumor DNA (ctDNA), and microvesicles, to better understand the correlation between biomarker expression and clinical outcomes.
This multicenter trial, with an estimated duration of four years, will be conducted at Institute of Cancer of the State of São Paulo (ICESP) and other partner institutions. The study aims to overcome existing barriers in rare cancer treatment by offering an innovative approach that explores the potential of personalized therapies based on molecular characteristics, rather than the tumor's primary site
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single-Arm Efficacy Study Nivolumab Treatment will be administered with intravenous nivolumab at a dose of 480 mg every 4 weeks. Treatment will continue until limiting toxicity, disease progression, or for a maximum of 12 months as maintenance if the individual achieves stable disease, partial response, or complete response.
- Primary Outcome Measures
Name Time Method Primary Objective 2 years Overall survival (in months) of patients with advanced or metastatic rare malignancies and CPS ≥ 10 following disease progression after prior treatments while receiving the anti-PD1 antibody Nivolumab.
Primary Endpoint 2 years The primary outcome of the study is the disease control rate (DCR) based on imaging, considering the best response to treatment. A response rate of 5% will be considered non-promising, and a response rate of 25% will be considered promising. The study follows Simon's two-stage design, with type I error (alpha) set at 0.05 and type II error (beta) at 0.10. In the first stage, if at least 1 out of the first 9 participants achieves disease control (stable disease, partial response, or complete response), 16 additional participants will be recruited for the second stage.
The study will be deemed positive if at least 3 out of 25 participants achieve disease control (partial response, complete response, or stable disease). A 10% drop-out rate (3 participants) is anticipated, bringing the maximum total recruitment to 28 participants.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) 2 years Percentage of patients with a tumor size reduction, measured according to RECIST criteria.
Subgroup Analysis Based on PD-L1 Expression and CPS: 2 years PD-L1 Expression: Proportion of patients showing PD-L1 positivity. CPS Subgroups: Proportion of patients with CPS between 10-20 and those with CPS \> 20.
Correlation of Clinical Outcomes with Biomarker Assessments 2 years Microvesicle Analysis: Correlation between clinical outcomes and levels of circulating microvesicles.
Serum Multiplex Panel: Correlation between clinical outcomes and serum biomarker levels (e.g., cytokines, chemokines), measured in concentration units (e.g., pg/mL).Overall Survival (OS) 2 years Time from treatment initiation to death from any cause, measured in months.
Progression-Free Survival (PFS) 2 years Time from treatment initiation to disease progression or death, whichever occurs first, measured in months.
Trial Locations
- Locations (8)
Hospital São Rafael
🇧🇷Salvador, Bahia, Brazil
Hospital São Carlos
🇧🇷Fortaleza, Ceará, Brazil
Hospital Santa Cruz
🇧🇷Curitiba, Paraná, Brazil
IDOR Recife
🇧🇷Recife, Pernambuco, Brazil
Instituto D'or de Pesquisa e Ensino
🇧🇷Sao Paulo, SP, Brazil
Instituto do Câncer do Estado de São Paulo - ICESP
🇧🇷São Paulo, SP, Brazil
DF Star
🇧🇷Brasília, Brazil
Instituto D'Or de Pesquisa e Ensino
🇧🇷Rio De Janeiro, Brazil